Summary Three cohorts of WTC rescue and recovery workers maintained at the Fire Department of the City of New York (FDNY), the Icahn School of Medicine at Mount Sinai (WTC General Responders Cohort, WTCGRC), and the New York City Department of Health and Mental Hygiene (WTC Health Registry, WTCHR) are currently engaged in a combined (pooled) analysis of cancer risk, latency and survival. Mortality among WTC rescue and recovery workers from the WTCHR and the WTCGRC cohorts, compared to the general population and based on relatively small numbers of deaths, showed a strong healthy worker effect HWE. This comparison can obfuscate increases in mortality due to WTC-related exposure. We propose to use the combined dataset of the three cohorts to analyze overall mortality and causes of death with sufficient number of events, taking advantage of the larger number of expected deaths and the additional time elapsed, and to use multiple causes of death. Specifically, we plan to perform a follow-up of mortality in a combined dataset of rescue and recovery workers from the three WTC cohorts, to use the combined WTC cohort to estimate overall mortality, and mortality from major causes, and to compare them to external reference rates. In addition, we plan to assess the role of WTC exposure in determining overall mortality and mortality from major causes among WTC rescue and recovery workers, and its possible interaction with other determinants of death (tobacco smoking, co-morbidities), in explaining the decreased mortality compared to the external reference populations. We further plan to estimate the temporal pattern of overall and cause-specific mortality in WTC rescue and recovery workers, notably whether mortality increases with time from the attacks. Finally, we plan to compare overall mortality and mortality from major causes of specific occupational groups within the WTC combined cohort, including police officers, firefighters, and construction workers, with other cohorts of the same groups of workers. The proposed analysis will provide strong evidence on the presence or absence of an association of WTC exposure and mortality among rescue/recovery workers, after accounting for other major determinants of mortality, and will inform on the best methodology to quantitative assess the effects of disasters on mortality of exposed individuals.